NH-BIS(一聚乙二醇-羟基) | 54384-47-3

• 分子结构分类: 有机化合物 - 有机氮化合物
• 中文名称: NH-BIS(一聚乙二醇-羟基)
• 英文名称: 3,9-dioxa-6-azaundecane-1,11-diol
• 英文别名: 6-aza-3,9-dioxaundecane-1,11-diol；NH-bis(PEG1-OH)；2-[2-[2-(2-hydroxyethoxy)ethylamino]ethoxy]ethanol
• CAS: 54384-47-3
• 化学式: C₈H₁₉NO₄
• 分子量: 193.243
• InChiKey: HPYJVTFKENYYFK-UHFFFAOYSA-N

物化性质

• 沸点：
  128 °C(Press: 0.02 Torr)
• 密度：
  1.090±0.06 g/cm3(Predicted)
• 溶解度：
  溶于水、DMSO、DCM、DMF

计算性质

• 辛醇/水分配系数(LogP)：
  -1.9
• 重原子数：
  13
• 可旋转键数：
  10
• 环数：
  0.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  71
• 氢给体数：
  3
• 氢受体数：
  5

安全信息

• 危险性防范说明：
  P264,P280,P302+P352,P337+P313,P305+P351+P338,P362+P364,P332+P313
• 危险性描述：
  H315,H319
• 储存条件：
  存储条件：2-8°C，干燥且密封。

制备方法与用途

生物活性 NH-bis-PEG2 是一种不可裂解 (non-cleavable) 的 2 单元 PEG 链接剂，用于抗体药物偶联物 (ADCs) 的合成。此外，它也是一种基于 PEG 的 PROTAC 链接剂，可用于 PROTAC 的合成。

靶点

不可裂解	PEGs

体外研究 ADCs 包含一种通过 ADC 链接剂连接到细胞毒性药物的抗体。PROTACs 则由两个不同配体通过链接剂相连组成；其中一个配体是 E3 泛素连接酶的配体，另一个则是目标蛋白的配体。PROTACs 通过利用细胞内的泛素-蛋白质体系统来选择性地降解目标蛋白。

反应信息

• 作为反应物：
  描述：

  NH-BIS(一聚乙二醇-羟基) 在 sodium hydride 作用下， 以 四氢呋喃 为溶剂， 反应 1.0h， 生成 9-Methoxymethyl-3,6,12,15-tetraoxa-9,21-diaza-bicyclo[15.3.1]henicosa-1(20),17(21),18-triene
  参考文献：
  名称：

  Synthesis of New Pyridinoazacrown Ethers Containing Aromatic and Heteroaromatic Proton Ionizable Substituents

  摘要：

  Methods for the synthesis of pyridinocrowns functionalized with various proton ionizable groups have been elaborated. Sixteen new ligands containing pyridine rings as part of the macrocycle or as a side arm have been prepared. Different interactive abilities of the OH and NH functions of 3,9-dioxa-6-azaundecane-1,11-diol (3) in strong base allowed the synthesis of pyridinoazacrowns 1 and 2 by cyclization with 2,6-bis((tosyloxy)methyl)pyridine (4) and THP-protected 4-hydroxy-2,6-bis(tosyloxy)methyl)pyridine (5). Pyridinoazacrown 1 was functionalized with different proton ionizable side arms by treatment first with formaldehyde in methanol to form the N-methoxymethyl derivative 6 and then treating 6 with 5-chloro-8-hydroxyquinoline or the appropriate substituted phenol. Pyridinoaza-18-crown-6 ligands containing p-methylphenol (7), p-methoxyphenol (8), p-chlorophenol (9),p-fluorophenol (10),p-cyanophenol (11), 2-formyl-4-bromophenol (12), or 5-chloro-8-hydroxyquinoline (13) groups were prepared by this process. Pyridinoazacrowns 1 and 2 were alkylated with 2-hydroxy-5-nitrobenzyl chloride or 5-chloro-8-methoxy-2-(bromomethyl)quinol followed by removal of the protecting groups to form p-nitrophenol- and 5-chloro-8-hydroxy-2-quinolinyl-substituted ligands (16, 18, and 21). Macrocycles 22 and 23 containing proton ionizable triazole and phenol functions inside the macrocyclic cavity and a pyridine side arm were prepared by cyclization of the appropriate dihalide with 6-(2'-pyridylmethyl)-3,9-dioxa-6-azaundecane-1,11-diol followed by cleavage of the THP or methoxy protecting groups. Preliminary complexation data show that the phenol-substituted pyridinoaza-18-crown-6 ligands form strong complexes with various metal cations and exhibit high selectivity toward Ag+. Macrocycle 16 containing a p-nitrophenol substituent formed a complex with benzylamine. The crystal structures for 16 and its benzylamine complex are also given here.

  DOI：

  10.1021/jo00124a022
• 作为产物：
  描述：

  2-氯乙氧基乙醇 在 氨 作用下， 以 乙醇 为溶剂， 生成 NH-BIS(一聚乙二醇-羟基)
  参考文献：
  名称：

  Oxetane function spiro to polyoxaaza macroheterocycles

  摘要：

  DOI：

  10.1021/jo00897a005

文献信息

• [EN] FLAVONOID DIMERS AND THEIR USE<br/>[FR] DIMÈRES FLAVONOÏDES ET LEURS APPLICATIONS
  申请人：UNIV MCGILL

  公开号：WO2011137516A1

  公开（公告）日：2011-11-10

  This invention relates to bis-flavonoid compounds of formula Flavonoid-Linker-Y-Linker-Flavonoid, their synthesis and use for inhibiting multidrug resistance in chemotherapy and protozoan infection.

  这项发明涉及到公式为黄酮素-连接子-Y-连接子-黄酮素的双黄酮类化合物，它们的合成以及在化疗和原虫感染中抑制多药耐药性的用途。
• Synthesis and characterization of a new macrobicyclic (Cryptand) siderophore containing three endocyclic hydroxamate donor groups
  作者：Yizhen Sun、Arthur E. Martell

  DOI：10.1016/s0040-4020(01)88367-8

  日期：1990.1

  The first trishydroxamate cryptand ligand was synthesized by tripodal coupling of a tris acid chloride and a tris O-benzylhydroxylamine. The spectrophotometric properties of its Fe(III) complex were investigated and compared with those of desferriferrioxamine B. Its 1:1 Ga(III) complex was also prepared and characterized.

  通过三酰氯和三O-苄基羟胺的三脚架偶合来合成第一三异羟肟酸酯的隐链配体。研究了它的Fe（III）配合物的分光光度特性，并与去铁敏草胺B进行了比较。还制备并表征了它的1：1 Ga（III）配合物。
• 四马来酰亚胺型连接子及其应用
  申请人：上海新理念生物医药科技有限公司

  公开号：CN107652219B

  公开（公告）日：2021-06-08

  本发明涉及四马来酰亚胺型连接子及其应用。特别地，本发明涉及式I所示的化合物，以及其作为连接子在制备抗体药物偶联物中的用途。通过该连接子制得的抗体药物偶联物具有较高的均一性和稳定性，可以有效用于肿瘤等各种疾病的治疗。式I中各基团的定义与说明书中相同。
• [EN] CONTRAST AGENTS<br/>[FR] AGENTS DE CONTRASTE
  申请人：BRACCO IMAGING SPA

  公开号：WO2017098038A1

  公开（公告）日：2017-06-15

  The present invention relates to new class of functionalized macrocycles capable of chelating paramagnetic metal ions, their chelated complexes with metal ions and the use thereof as contrast agents, particularly suitable for Magnetic Resonance Imaging (MRI) analysis.5

  本发明涉及一类新型的功能化大环化合物，能够螯合顺磁性金属离子，以及它们与金属离子形成的螯合络合物，以及将其用作对比剂的用途，特别适用于磁共振成像（MRI）分析。
• Synthesis of Monoaza Crown Ethers from<i>N</i>,<i>N</i>-Di[oligo(oxyalkylene)]amines and Oligoethylene Glycol Di(<i>p</i>-toluenesulfonates) or Corresponding Dichlorides
  作者：Hirokazu Maeda、Shigeo Furuyoshi、Yohji Nakatsuji、Mitsuo Okahara

  DOI：10.1246/bcsj.56.212

  日期：1983.1

  Monoaza crown ethers were prepared in satisfactory yields by the one-step reaction between diethanolamine or N,N-di[oligo(oxyethylene)]amines and oligoethylene glycol di(p-toluenesulfonates) or corresponding dichlorides in t-butyl alcohol/dioxane in the presence of sodium or potassium t-butoxide. The reaction conditions in the preparation of monoaza 15- and 18-crown ethers were studied. Various monoaza

  通过二乙醇胺或 N,N-二[低聚(氧乙烯)]胺与低聚乙二醇二(对甲苯磺酸盐)或相应的二氯化物在叔丁醇/二恶烷中的一步反应制备了单氮杂冠醚，收率令人满意。存在叔丁醇钠或钾。研究了制备单氮杂15-和18-冠醚的反应条件。还制备了各种具有取代基的单氮杂冠醚并研究了它们的性质。